New Oral Anticoagulants for Venous Thromboembolism Prophylaxis in Total Hip and Knee Arthroplasty: A Systematic Review and Network Meta-Analysis

Background: There is controversy over whether use of new oral anticoagulants (NOACs) associates with increased hemorrhage risk compared with non-NOAC. Meanwhile, determining which NOAC to use remains unclear. We aimed to summarize the evidence about NOACs in venous thromboembolism (VTE) prevention for patients with total hip and knee arthroplasty (THA and TKA).Methods: We searched RCTs assessing NOACs for VTE prophylaxis in adults undergoing THA and TKA in Medline, Embase, and Cochrane up to May 2021. Primary outcomes were VTE [included deep vein thrombosis (DVT) and pulmonary embolism (PE)], major VTE, and major bleeding. The rank probabilities of each treatment were summarized by the surface under the cumulative ranking curve area (SUCRA).Results: 25 RCTs with 42,994 patients were included. Compared with non-NOAC, NOACs were associated with a decreased risk of VTE (RR 0.68; 95% CI 0.55–0.84) and major VTE (RR = 0.52; 95% CI 0.35–0.76). Additionally, rivaroxaban, apixaban, and edoxaban but not dabigatran and betrixaban, did confer a higher efficacy compared with non-NOAC. None of the individual NOACs increased the risk of bleeding, while apixaban and betrixaban were even associated with a decreased risk of bleeding. In the comparison of different NOACs, rivaroxaban was associated with the greatest benefits in VTE (SUCRA = 79.6), DVT (SUCRA = 88.8), and major VTE (SUCRA = 89.9) prevention. Furthermore, subgroup analysis confirmed that NOACs associated with a higher efficacy tendency in patients with follow-up duration <60 days than follow-up duration ≥60 days.Conclusion: Evidence suggests that NOACs exert more benefits on VTE prophylaxis, and none of the individual NOACs increased hemorrhage compared with non-NOAC. Among various NOACs, rivaroxaban is recommended in patients with lower bleeding risk, and apixaban is recommended in patients with higher bleeding risk.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021266890].

Efficacy and Safety of Enoxaparin versus New Oral Anticoagulants to Prevent Venous Thromboembolism after Total Hip Replacement: A Systematic Review and Meta-Analysis

Prophylactic anticoagulant therapy is recommended for reducing the risk of venous thromboembolism (VTE) after a total hip replacement (THR). However, it is not clear which anticoagulant is preferable. Hence, a systematic review and meta-analysis of randomized double-blind controlled trials (RDBCTs) were conducted to investigate the clinical efficacy and safety of enoxaparin in comparison with newer oral anticoagulants for the prevention of VTE after THR. The Cochrane Library, Scopus, Web of Science, Embase, and PubMed/Medline databases were used for PICO search strategy. Relative risks (RR) of symptomatic VTE, clinically relevant bleeding, mortality, and a net clinical endpoint were estimated employing a random effect meta-analysis. ITC and RevMan software were used for indirect and direct comparisons, respectively. Nine RDBCTs comprising 24,584 patients were included. As compared to enoxaparin, a reduced risk for symptomatic VTE was observed with rivaroxaban (confidence interval [CI]: 0.32–0.77; RR: 0.46%) and comparable with apixaban (0.12–1.26; 0.42%) and dabigatran (0.22–2.20; 0.70%). Contrarily to enoxaparin, a greater risk for clinically relevant bleeding was observed with rivaroxaban (1.03–1.48; 1.23%), comparable with dabigatran (0.96–1.33; 1.10%) and reduced with apixaban (0.19–5.66; 0.96%). In indirect or direct comparisons, the interventions did not differ on the net clinical endpoint. In conclusion, the findings of this meta-analysis revealed no significant difference in the efficacy and safety of new oral anticoagulants as compared to enoxaparin for the prevention of VTE after total hip replacement surgery.